Suppression of fever in rabbits by a protein synthesis inhibitor, anisomycin.

Abstract

The protein synthesis inhibitor anisomycin was given into the cerebral ventricles of rabbits as a priming dose followed by a continuous infusion. Doses of 100, 200 and 300 .mu.g followed by infusions at 100, 200 and 300 .mu.g/h inhibited the incorporation of [14C] leucin into hypothalamic protein by > 90%. Injection and infusion of anisomycin (300 .mu.g) suppressed the febrile response to leukocyte (endogenous) pyrogen administered i.v. or intracerebroventricularly. Dialysis experiments showed that anisomycin did not combine irreversibly with leukocyte pyrogen. Anisomycin did not intefere with thermoregulation in a cold environment. Pyrogenesis may involve a step which is dependent on synthesis of hypothalamic protein with a rapid turnover.